This is a renewal application for support of the Yale University Digestive Disease Research Core Center, a multi-disciplinary Center whose research focus is Liver Structure, Function and Disease. Thirty-five independently funded investigators comprise a research based of approximately $8.5 million. Current research programs in the Center are distributed in 10 departments of the University including Biology, Cell Biology, Cellular and Molecular Physiology, Epidemiology and Public Health, Human Genetics, Medicine, Pathology, Pediatrics, Pharmacology and Surgery. The research based focuses on six major areas: 1) Cellular and Molecular Biology of the Liver, 2) Hepatic Transport Mechanisms, 3) Basic Biology of Disease Processes, 4) Studies of the Hepatic and Splanchnic Circulation, 5) Clinical Hepatology, and 5) Liver Immunology. The research programs in the Center are quite broad and range from fundamental studies of the biology of liver research programs in the Center are quite broad and range from fundamental studies of the biology of liver cells to clinical therapeutic trials of immediate clinical relevance to the diagnosis and treatment of chronic liver cells to clinical therapeutic trials of immediate clinical relevance to the diagnostic and treatment of chronic liver cells to clinical therapeutic trials of immediate clinical relevance to the diagnosis and treatment of chronic liver cells to clinical therapeutic trials of immediately clinical relevance to the diagnosis and treatment of chronic liver disease in patients with these disorders. The major goals of the Center continue to be: 1) to stimulate multi-disciplinary interactions between basic and clinical faculty and departments, 2) to provide in-depth training environment, 3) to efficiently organize time consuming, often costly techniques and procedures in core facilities for use by multiple investigators, 4) to stimulate basic scientists to direct their talents and technologies to specific areas of research interest in the Center, 5) to promote important new research and training opportunities through a pilot feasibility project program, and 6) to create an intellectual environment within opportunities through a pilot feasibility project program, and 6) to create an intellectual environment within the institution in the field of Hepatology and to foster collaborations both within and outside the institution. To achieve these goals the Center is organized into five Core Facilities including both within and outside the institution. To achieve these goals the Center is organized into five Core Facilities including: 1) Administrative Core, 2) Cell Isolation, Culture and Organ Perfusion Core, 3) Molecular Biology Core, and 4) Imaging Core. A Pilot Feasibility Program supports small 1-2 year grants for new scientific initiatives. An Enrichment program consists of a seminar program, journal clubs, symposia, retreats and Center newsletters.